Numerous epidemiological studies report an inverse relationship between low birth weight (LBW) and the risk of hypertension; however, the mechanisms linking LBW and hypertension remain unclear. The kidneys are known to play an important role in the long-term regulation of arterial pressure. An important role for the kidneys in the programming of hypertension is suggested as maternal protein restriction administered during nephrogenesis or the last third of gestation in the rat, results in hypertensive LBW offspring that are associated with alterations in the renin angiotensin system (RAS) and the sympathetic nervous system (SNS). Thus, animal models of fetal malnutrition induced by maternal protein restriction during gestation support a role for programming of hypertension due to an adverse fetal environment. In humans, fetal malnutrition, due to either an insufficient nutrient delivery via reduced uteroplacental perfusion or maternal undernutrition, limits fetal growth and results in small-for-gestational-age newborn. As LBW within the Western world is more likely the result of impaired uteroplacental perfusion rather than maternal malnutrition, we have developed a unique model of in vivo placental insufficiency to examine the association between LBW and hypertension. Specifically, reduced uterine perfusion induced during late gestation in the rat results in LBW offspring born at term that develop hypertension, and based on preliminary data, exhibit alterations in both the RAS and SNS. Thus, adaptations to oxygen and nutrient restriction during a critical period of fetal development may lead to programming with resulting activation of the RAS and SNS leading to the development of hypertension. Thus, we will utilize our novel animal model to test the central hypothesis that hypertension in LBW offspring is initiated and sustained by abnormalities in the RAS and the SNS. To test this hypothesis, we plan to characterize temporal changes in the RAS and SNS, and directly assess the role of these systems in the pathogenesis of the hypertension utilizing molecular and physiological methods. Specific aims to be addressed are: 1. To test the hypothesis that abnormalities in the RAS mediate the hypertension in LBW offspring. 2. To test the hypothesis that abnormalities in the SNS mediate the hypertension in LBW offspring. 3. To determine the temporal interactions between the SNS and the RAS in mediating hypertension in LBW offspring. [unreadable] [unreadable]